Hino Satoshi, Kawamata Hitoshi, Omotehara Fumie, Uchida Daisuke, Miwa Yoshihiro, Begum Nasima-Mila, Yoshida Hideo, Sato Mitsunobu, Fujimori Takahiro
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, 3-18-15 Kuramoto, Tokushima, 770-8504, Japan.
Biochem Biophys Res Commun. 2002 Apr 12;292(4):957-63. doi: 10.1006/bbrc.2002.6776.
We transfected a salivary gland cancer cell line, TYS, with three different forms of TSC-22 (transforming growth factor-beta-stimulated clone-22) gene: full-length TSC-22 (TSC-22FL) containing nuclear export signal, TSC-box and leucine zipper, truncated TSC-22 (TSC-22LZ) containing only TSC-box and leucine zipper, and truncated TSC-22 with nuclear localization signal (NLS-TSC-22LZ). High expression of TSC-22FL in the cytoplasm markedly enhanced the radiation-sensitivity of TYS cells, while, moderate expression of TSC-22FL marginally affected the radiation-sensitivity. TSC-22LZ, which was expressed in the cytoplasm and the nucleus, enhanced the radiation-sensitivity of TYS cells irrespective to its expression level. NLS-TSC-22LZ, which was expressed only in the nucleus, marginally affected the radiation-sensitivity of the cells even at high expression level. Interestingly, cytoplasmic TSC-22 translocates to nucleus concomitant with radiation-induced apoptosis. These results suggest that cytoplasmic localization of TSC-22 and translocation of TSC-22 from cytoplasm to nucleus is important for regulating the cell death signal after irradiation-induced DNA damage.
我们用三种不同形式的TSC - 22（转化生长因子β刺激克隆-22）基因转染了一种唾液腺癌细胞系TYS：包含核输出信号、TSC框和亮氨酸拉链的全长TSC - 22（TSC - 22FL），仅包含TSC框和亮氨酸拉链的截短型TSC - 22（TSC - 22LZ），以及带有核定位信号的截短型TSC - 22（NLS - TSC - 22LZ）。TSC - 22FL在细胞质中的高表达显著增强了TYS细胞的辐射敏感性，而TSC - 22FL的适度表达对辐射敏感性影响较小。在细胞质和细胞核中均有表达的TSC - 22LZ，无论其表达水平如何，都增强了TYS细胞的辐射敏感性。仅在细胞核中表达的NLS - TSC - 22LZ，即使在高表达水平时，对细胞的辐射敏感性影响也较小。有趣的是，细胞质中的TSC - 22会随着辐射诱导的凋亡而转移至细胞核。这些结果表明，TSC - 22的细胞质定位以及TSC - 22从细胞质向细胞核的转移对于调节辐射诱导的DNA损伤后的细胞死亡信号很重要。
